Genetic analysis

Title: Genetic analysis.Abstract: The present invention provides methods for generating genetic profiles or analyses. Included are methods for conducting comprehensive, dynamic genetic analysis. Also provided are methods for determining genetic health scores for specific phenotypes, such as diseases, disorders, traits, and conditions, as well as for organ systems, for certain medical specialties, and for overall health. ...

This application claims the benefit of U.S. Provisional Application No. 61/037,959 filed Mar. 19, 2008, U.S. Provisional Application No. 61/050,126 filed May 2, 2008, U.S. Provisional Application No. 61/091,342 filed Aug. 22, 2008, U.S. Provisional Application No. 61/136,266 filed Aug. 22, 2008, and U.S. Provisional Application No. 61/198,765 filed Nov. 7, 2008, all of which are incorporated herein by reference in their entirety. This application relates to U.S. patent application Ser. No. ______, entitled “Genetic Analysis,” Attorney Docket No. 35925-702.202; U.S. patent application Ser. No. ______, entitled “Genetic Analysis,” Attorney Docket No. 35925-702.203; and U.S. patent application Ser. No. ______, entitled “Genetic Analysis,” Attorney Docket No. 35925-702.204, all of which are concurrently filed in the U.S. Patent and Trademark Office on Mar. 18, 2009, and all of which are hereby incorporated herein by reference in their entirety. This application also relates to International Application No. ______, entitled “Genetic Analysis,” Attorney Docket No. 35925-702.601, which is concurrently filed in the U.S. Receiving Office on Mar. 18, 2009, and which is hereby incorporated herein by reference in its entirety.

BACKGROUND

The genomes of organisms contain a vast amount of information that can be mined in order to predict, identify or describe observable characteristics of an organism, such as diseases, conditions, disorders, traits, characteristics, morphology, biochemical properties, or physiologic properties. Observable characteristics can also be affected, determined, or predicted from environmental conditions, or from some combination of genetic and environmental conditions. There is an unmet need for an intelligent approach to using genetic and non-genetic information to predict, identify, analyze or describe phenotypes in an organism.

SUMMARY

A first aspect provided herein is a method of determining an organ system score of an individual comprising: identifying a set of genetic variants in an individual, wherein said genetic variants relate to an organ system phenotype; calculating the predisposition or carrier status of said individual for at least two phenotypes wherein said predisposition or carrier status is based on said set of genetic variants; combining the results of the previous step to obtain an organ system score; and, reporting said organ system score to said individual, a health care provider of said individual, or a third party.

A second aspect provided herein is a method of determining an overall genetic health score of an individual comprising: identifying a set of genetic variants in an individual; calculating two or more organ system scores according to the first 3 steps of the first aspect; combining said two or more organ system scores to obtain an overall genetic health score; and, reporting said overall genetic health score in a report to said individual, a health care provider of said individual, or third party.

In some embodiments of the methods of the first two aspects, said organ system score in said report is divided into two or more specific medical phenotypes. In other embodiments of the methods provided at least one of said medical phenotypes is a rare disease. In further embodiments of the methods provided, at least one of said medical phenotypes follows monogenic inheritance. In another embodiment of the methods provided, at least one of said medical phenotypes follows multifactorial or polygenic inheritance. In yet another embodiment of the methods provided, at least one of said medical phenotypes follows monogenic inheritance; and at least one of said medical phenotypes follows multifactorial or polygenic inheritance.

In an embodiment of the methods of the first two aspects, said reporting is by e-mail, a website, paper, or in person. In an embodiment of the methods of the first two aspects, said reporting is by transmission over a network. In some embodiments of the methods of the first two aspects, the methods further comprise providing a pedigree analysis of said individual to said individual, a health care provider of said individual, or third party. In some embodiments of the methods of the first two aspects, the methods further comprise providing a medical recommendation based on said score by a physician to said individual, a health care provider of said individual, or third party. In other embodiments, said physician is a medical specialist. In further embodiments, said medical specialist is selected from the group consisting of: anesthesiologist, cardiologist, dermatologist, endocrinologist, gastroenterologist, hematologist, infectious disease specialist, immunologist, fertility specialist, men's health specialist, nutrition and obesity specialist, neurologist, obstetrician, gynecologist, oncologist, ophthalmologist, pediatrician, pharmacologist, psychiatrist, pulmonologist, rheumatologist, surgeon, urologist, and women's health specialist.

In some embodiments of the methods of the first two aspects, said set of genetic variants comprises genetic variants for at least 1500 genes. In other embodiments of the methods of the first two aspects, said set of genetic variants comprises at least two genetic variants, each of which is correlated to the same phenotype. In some embodiments of the methods of the first two aspects, said set of genetic variants comprises at least 5000 single nucleotide polymorphisms. In some embodiments of the methods of the first two aspects, said set of genetic variants comprises at least 50 single nucleotide polymorphisms, wherein each SNP is correlated to a medical phenotype. In some embodiments of the methods of the first two aspects, said set of genetic variants comprises at least one SNP sequence not listed in a public database, wherein said at least one SNP sequence is correlated to a medical phenotype.

In some embodiments of the methods of the first two aspects, calculating of said score includes the gender, ethnicity, age, weight, lifestyle habits, medications, alternative therapies, family history of disease and/or personal history of disease of said individual. In some embodiments of the methods of the first two aspects, said reporting is performed within one week of the first step. In some embodiments of the methods of the first two aspects, said reporting is performed only when a decreased predisposition for said phenotype is determined. In some embodiments of the methods of the first two aspects, said reporting is performed only when an increased predisposition for said phenotype is determined. In some embodiments of the methods of the first two aspects, said individual selects said at least two phenotypes.

In some embodiments of the methods of the first two aspects, said calculating is performed by consulting a database comprising at least one medical or scientific article about a clinical study that shows a correlation or association between at least one genetic variant and at least one phenotype. In an embodiment of the methods, said medical or scientific article is ranked against other medical or scientific articles based on one or more of the following factors: the number of people in the disease cohort of said clinical study, the number of people in control cohort of said clinical study, the total number of people in said clinical study, the caliber of the institution that conducted said clinical study, the place said clinical study was conducted, the year said clinical study was published, the reputation of any of the authors of said clinical study, and the rating of the journal where said medical or scientific article appeared. In some embodiments of the methods, rating of said journal is based on one or more of the following factors: the Impact Factor of said journal, the Immediacy Index of said journal, the cited half-life of said journal, and the Page Rank of said journal.

In further embodiments of the methods of the first two aspects, calculating is performed by consulting a database comprising a ranking system that rates genetic variants based on the relative strength of the data reported from clinical studies. In another embodiment, calculating excludes a genetic variant in linkage disequilibrium with a genetic variant with a higher rating as determined by said ranking system. In other embodiments, said ranking system is based on one or more of the following factors: the number of clinical studies reporting a correlation or association between said at least one genetic variant and said at least one phenotype; the number of studies showing contradictory results regarding said correlation or association; the aggregate number of people participating in said clinical studies; the type of study conducted; the degree to which the study has been replicated; and the year the study was conducted.

In some embodiments of the methods of the first two aspects, said calculating is performed by consulting a database comprising a ranking system that rates genetic variants based on the relative clinical value of the association between the genetic variant and the phenotype. In an embodiment, relative clinical value is determined by one or more medical specialists. In some embodiments, relative clinical value is determined by one or more: licensed physician, anesthesiologist, cardiologist, dermatologist, endocrinologist, gastroenterologist, hematologist, infectious disease specialist, immunologist, fertility specialist, men's health specialist, nutrition and obesity specialist, neurologist, obstetrician, gynecologist, oncologist, ophthalmologist, pediatrician, pharmacologist, psychiatrist, pulmonologist, rheumatologist, surgeon, urologist, and women's health specialist. In some embodiments of the methods of the first two aspects, said methods are performed at a health club, spa, medical center, or rehabilitation center. In some embodiments of the methods of the first two aspects, said set of genetic variants is generated using at least one panel from FIGS. 15-73, 75-149.

A third aspect provided herein is a method of determining and reporting the predisposition or carrier status of an individual for a reflex phenotype comprising: a) identifying a set of genetic variants in an individual, wherein each of said genetic variants is correlated with a phenotype; b) determining the predisposition or carrier status of said individual to an initial phenotype and to a reflex phenotype, wherein said predisposition or carrier status is based on said set of genetic variants; and c) reporting said predisposition or carrier status to said individual, to a health care provider of said individual, or to a third party, wherein the reporting of the predisposition or carrier status to the reflex phenotype depends on the outcome of said determination of predisposition or carrier status to the first phenotype.

In an embodiment, said reflex phenotype is reported when said individual is predisposed to, at risk of, or a carrier of said initial phenotype. In some embodiments, said reflex phenotype is reported when said individual is not predisposed to, at risk of, or a carrier of said initial phenotype. In some embodiments, said reflex phenotype is reported concurrently with said initial phenotype. In other embodiments, said reflex phenotype is reported subsequently to said initial phenotype. In further embodiments, said reflex phenotype is not reported when said individual is not predisposed to, at risk of, or a carrier of said initial phenotype. In another embodiment, said reflex phenotype is a phenotype that is not the initial phenotype.

In an embodiment, said determining of the predisposition or carrier status of the individual to said reflex phenotype is determined subsequently to the determining of the predisposition or carrier status of the individual for said initial phenotype. In some embodiments, said reflex phenotype is a disease that is positively correlated with said initial phenotype. In some embodiments, said initial phenotype is a disease and said reflex phenotype is a symptom or sequela of said disease. In other embodiments, said initial phenotype is a disease or disorder and said reflex phenotype is a side effect of, or response to, a treatment for said initial phenotype. In other embodiments, said predisposition or carrier status is determined from at least two genetic variants. In further embodiments, at least two genetic variants are correlated with the same phenotype.

A fourth aspect provided is a method of predicting a genetic predisposition or carrier status of a potential offspring comprising: a) identifying one or more genetic variants in the genome of the potential mother of a potential offspring, or obtaining one or more previously-identified genetic variants in the genome of the potential mother, wherein each of the genetic variants is associated with a phenotype; b) identifying one or more genetic variants in the genome of the potential father of a potential offspring, or obtaining one or more previously-identified genetic variants in the genome of the potential father, wherein each of the genetic variants is associated with a phenotype; c) based on the set of genetic variants, calculating the predisposition or carrier status of the potential offspring's mother for the phenotype; d) calculating the predisposition or carrier status of the potential offspring's father for the phenotype wherein the predisposition or carrier status is based on the set of genetic variants; e) calculating the potential offspring's predisposition or carrier status for the phenotype wherein the calculating is based on combining the results of step c) and d); and, optionally, f) repeating steps a) through e), wherein the potential mother is different from the potential mother of step a), or wherein the potential father is different from the potential father of step b). In an embodiment, the predisposition is the highest potential risk. In an embodiment, the predisposition is the lowest potential risk.

In an embodiment of the fourth aspect, the method further comprises identifying or obtaining the genetic location of the genetic variants of step a) and step b), wherein said genetic location is an autosomal chromosome, a non-autosomal chromosome, or mitochondrial chromosome. In some embodiments of the fourth aspect, the method further comprises the steps of adjusting the result of step c) in light of the results obtained in the previous embodiment and adjusting the result of step d) in light of the results obtained in the previous embodiment. In other embodiments of the fourth aspect, said identifying is by nucleic acid array or sequencing apparatus.

In further embodiments of the fourth aspect, the potential mother in step f) is the same as the potential mother in step a) and the potential father in step f) is different from the potential father in step b) and the method further comprising the step of comparing the result from step e) with the result from step f). In a specific embodiment, the method further comprises the step of identifying the potential father of a potential offspring with the highest risk or predisposition for a phenotype.

In yet further embodiments of the fourth aspect, the potential father in step f) is the same as the potential father in step b) and the potential mother in step f) is different from the potential mother in step a) and the method further comprising the step of comparing the result from step e) with the result from step f). In an embodiment of the fourth aspect, the method further comprises the step of repeating step f) one or more times. In a specific embodiment, the method further comprises the step of identifying the potential mother of a potential offspring with the highest risk or predisposition for a phenotype.

In some embodiments of the fourth aspect, the potential mother in step a) and the potential father in step b) are both humans. In other embodiments of the fourth aspect, the potential mother in step a) and the potential father in step b) are both cows. In other embodiments of the fourth aspect, the potential mother in step a) and the potential father in step b) are both horses. In further embodiments of the fourth aspect, the potential mother in step a) and the potential father in step b) are both pigs. In another embodiment of the fourth aspect, the potential mother in step a) and the potential father in step b) are both dogs. In yet another embodiment of the fourth aspect, the potential mother in step a) and the potential father in step b) are both sheep. In some embodiments of the fourth aspect, the potential mother in step a) and the potential father in step b) are both mammals. In other embodiments of the fourth aspect, the potential mother in step a) and the potential father in step b) are both plants.

In an embodiment of the fourth aspect wherein the method further comprises identifying or obtaining the genetic location of the genetic variants of step a) and step b), wherein said genetic location is an autosomal chromosome, a non-autosomal chromosome, or mitochondrial chromosome, the method also further comprises the step of identifying the potential father of a potential offspring with the highest risk or predisposition for a phenotype.

A fifth aspect provided herein is an array comprising at least 100 oligonucleotide sequences attached to a support, wherein each of said sequences is associated with a genetic variant, and the majority of said genetic variants are linked to at least one citation for a peer-reviewed scientific article correlating said genetic variant to a medical phenotype or trait. In an embodiment of the array, each of said genetic variants is correlated to a medical phenotype.

A sixth aspect provided herein is an array comprising at least 100 oligonucleotide sequences attached to a support, wherein at least 5% of said sequences are not listed in a public database, and each of said sequences is associated with a genetic variant correlated to a medical phenotype.

A seventh aspect provided herein is an array comprising at least 100 oligonucleotide sequences attached to a support, wherein each of said sequence is used to determine an organ system score for an individual. In an embodiment, of the array, said organ system is selected from the group consisting of: cardiovascular; dermatology; development and learning; ear, nose throat and dental; endocrinology; gastroenterology and hepatology; gynecology; hematology and oncology; immunology and allergy; infectious diseases; men's health; metabolic and rare diseases; musculoskeletal; neonatology; neurology; obstetrics; ophthalmology; pharmacology, toxicology and anesthesiology; psychiatry; rheumatology; sexuality and fertility; sleep medicine; surgery; syndromes; traits and special abilities; urology and nephrology; vascular; and women's health.

An eighth aspect provided herein is an array comprising at least 100 oligonucleotide sequences attached to a support, wherein each of said sequences is linked to at least one recommendation by a medical specialist. In some embodiments of the array, said medical specialist is selected from the group consisting of: anesthesiologist, cardiologist, dermatologist, endocrinologist, gastroenterologist, hematologist, infectious disease specialist, immunologist, fertility specialist, men's health; specialist, nutrition and obesity specialist, neurologist, obstetrician, gynecologist, oncologist, ophthalmologist, pediatrician, pharmacologist, psychiatrist, pulmonologist, rheumatologist, surgeon, urologist, and women's health specialist.

A ninth aspect provided herein is a system comprising: a database comprising at least 100 oligonucleotide sequences attached to a support, wherein each of said sequences are associated with a genetic variant; code for linking each of said sequences to at least one medical recommendation by a medical specialist; and, code for generating a report comprising said medical recommendation.

A tenth aspect provided herein is a system comprising: a database comprising at least 100 oligonucleotide sequences attached to a support, wherein each of said sequences are associated with a genetic variant; code for calculating one or more organ system scores based on said sequences; and, code for generating a report comprising said score.

In some embodiments of the ninth and tenth aspects is a system further comprising: code linking each of said sequences to at least one citation for a peer-reviewed scientific article correlating said genetic variant to a medical phenotype or trait. In some embodiments of the ninth and tenth aspects is a system, each of said genetic variants is correlated to a medical phenotype. In other embodiments, at least one of said medical phenotypes is a rare disease. In further embodiments, at least one of said medical phenotypes is a monogenic phenotype. In another embodiment, at least one of said medical phenotypes is a multifactorial phenotype.

In some embodiments of the ninth aspects said organ system is selected from the group consisting of: cardiovascular; dermatology; development and learning; ear, nose throat and dental; endocrinology; gastroenterology and hepatology; gynecology; hematology and oncology; immunology and allergy; infectious diseases; men's health; metabolic and rare diseases; musculoskeletal; neonatology; neurology; obstetrics; ophthalmology; pharmacology, toxicology and anesthesiology; psychiatry; rheumatology; sexuality and fertility; sleep medicine; surgery; syndromes; traits and special abilities; urology and nephrology; vascular; and women's health.

An eleventh aspect provided herein is a computer readable medium, comprising a set of instructions to cause a computer to perform the steps of comparing input data comprising genetic variant information from an individual's genome against a set of data comprising association data correlating genetic variants with phenotypes and generating an output comprising an evaluation of the predisposition, or carrier status, of said individual for at least two phenotypes.

An twelfth aspect provided herein is a computer program product comprising a computer readable medium having computer program logic recorded therein for enabling a processor to determine the genetic predisposition or carrier status of a subject, said computer logic comprising: a) a storing procedure that enables the processor to store a set of information comprising a set of correlations, wherein each correlation comprises a correlation between a genetic variant and a phenotype; b) a receiving procedure that enables the processor to receive a set of information comprising one or more genetic variants within the genome of a subject; c) a comparing procedure to compare input data from the genome of said subject against the set of information in step a); d) a calculating procedure to calculate one or more scores based on said genetic variants within the genome of said subject; and e) an output procedure to provide a report of said comparison.

In some embodiments of the computer program product of the eleventh and twelfth aspects, the computer program product further comprising: a linking procedure linking each of said genetic variants to at least one citation for a peer-reviewed scientific article correlating said genetic variant to a medical phenotype. In some embodiments of the computer program product of the eleventh and twelfth aspects, at least one of said medical phenotypes follows monogenic inheritance and at least one of said medical phenotypes follows multifactorial or polygenic inheritance.

A thirteenth aspect provided herein is a method of selecting a haploid genome containing cell comprising: applying a sample from said cell to an array; and, determining a set of genetic variants of said cell. In an embodiment, said cell is of male origin. In some embodiments, said cell is of female origin. In some embodiments, said cell is an oocyte. In some embodiments, said cell is a sperm cell. In other embodiments, the method further comprises selecting said haploid genome containing cell to produce a diploid embryo. In further embodiments, the method further comprises incorporating one or more factors chosen from the gender, ethnicity, age, weight, lifestyle habits, medications, alternative therapies, family history of disease and personal history of disease of the donor of said haploid genome containing cell.

A fourteenth aspect provided herein is an array comprising at least one oligonucleotide for detecting a degree of risk to an initial phenotype and a second oligonucleotide for detecting a degree of risk to a reflex phenotype. In an embodiment, said initial phenotype is a disease or disorder and said reflex phenotype is the response to or effectiveness of a drug for treating said disease or disorder. In some embodiments, said initial phenotype is cancer and said reflex phenotype is the response to a cancer drug. In some embodiments, said cancer is breast cancer and said cancer drug is tamoxifen. In other embodiments, said initial phenotype is addiction and said reflex phenotype is a disease associated with said addiction. In further embodiments, said addiction is nicotine addiction and said disease associated with said addiction is lung cancer.

In some embodiments, the genetic variants are present in nucleic acids provided from the individual as a sample, which sample may have been previously obtained, i.e. prior to performance of the methods provided herein. In some embodiments, the genetic variants are present in an individual's genome or nucleic acids provided by the individual or a third party as a sample, which sample may have been previously obtained, i.e. prior to performance of the methods provided herein.

One aspect provides a nucleic acid sample from an individual for use in a method of determining the risk, predisposition, or carrier status of that individual for one or more phenotypes, the method comprising: identifying by nucleic acid array or sequencing apparatus one or more genetic variants in an individual or a set of genetic variants in an individual, wherein each of said genetic variants is correlated with a phenotype; using a computer to determine the predisposition of said individual for a phenotype wherein said predisposition is based on said set of genetic variants or said one or more genetic variants; and, optionally, providing a report of said predisposition to said individual.

Another aspect provided herein is related to gender specific health phenotypes and is a method of determining the predisposition or carrier status of an individual for two or more gender specific health phenotypes comprising: identifying by nucleic acid array; sequencing apparatus, or nanopore sequencer a set of genetic variants in an individual, wherein each of said genetic variants is correlated with a gender-specific health phenotype; using a computer to determine the predisposition or carrier status of said individual for at least two phenotypes, wherein said predisposition or carrier status is based on said set of genetic variants; providing a report of said predisposition or carrier status to said individual, to a health care provider of said individual, or to a third party; and optionally combining the predisposition or carrier status of said individual for said at least two phenotypes into a gender-specific health score, wherein said score is reported to said individual, to a health care provider, or to a third party.

In an embodiment of the gender specific health aspect, at least two phenotypes comprise an initial phenotype and a reflex phenotype, wherein said reflex phenotype is a phenotype that is not the initial phenotype, and wherein the reporting of the predisposition or carrier status of said individual for the reflex phenotype depends on the outcome of said determination of predisposition or carrier status of said individual for the first phenotype. In some embodiments, at least two phenotypes are at least two phenotypes listed in one or more of the following figures: Women's Health Panel Alpha (FIG. 19), Women's Health Panel Beta (FIG. 20), Female Fertility Panel (FIG. 30) Gynecology Panel (FIG. 56), Polycystic Ovary Syndrome Panel (FIG. 128), Men's Health Panel Alpha (FIG. 21), Men's Health Panel Beta (FIG. 22), Male Fertility & Erectile Function Panel (FIG. 31); Urology & Nephrology Panel (FIG. 61), Sexuality, or Mate Selection, Relationships and Marriage/Divorce Panel (FIG. 36). In other embodiments, at least two phenotypes comprise at least five phenotypes. In further embodiments, at least two phenotypes comprise: at least one phenotype that follows monogenic inheritance; and at least one phenotype that follows multifactorial or polygenic inheritance.

In other embodiments of the gender specific health aspect, at least two phenotypes comprises at least two of the following phenotypes: polycystic ovary syndrome; ovulatory response to metformin treatment of polycystic ovary syndrome; symptomatology with polycystic ovary syndrome; or metabolic syndrome or impaired fasting glucose with polcystic ovary syndrome. In further embodiments, at least two phenotypes comprises at least two of the following phenotypes: male fertility or infertility; heart disease; thrombophilia or thromboembolic disease; cardiac arrhythmia or cardiac conduction abnormality; cancer of male reproductive organs; skin cancer or sensitivity to ultraviolet light; lung cancer; colorectal cancer; Alzheimer's disease; hypertension or blood pressure level; or stroke.

In another embodiment of the gender specific health aspect, at least two phenotypes comprises at least two of the following phenotypes: myocardial infarction; melanoma; colorectal cancer; prostate cancer; androgenic alopecia; erectile dysfunction medication treatment effectiveness or sensitivity; thrombophila or thromboembolic disease; lumbar disc disease; Alzheimer's disease; or arrhythmogenic right ventricular cardiomyopathy. In yet another embodiment, at least two phenotypes comprises at least two of the following phenotypes: male fertility or infertility; erectile dysfunction medication treatment, effectiveness or sensitivity; peripheral arterial disease; fetal viability; primary or secondary sex characteristics, sex reversal or hypogonadism; or hypogonadism.

In an embodiment of the gender specific health aspect, at least two phenotypes comprises at least two of the following phenotypes: male fertility or infertility; erectile dysfunction medication treatment, effectiveness or sensitivity; prostate cancer; nephrolithiasis or urolithiasis; bladder cancer, kidney cancer, or adrenal cancer; IgA nephropathy; diabetic nephropathy; polycystic kidney disease; or risk of complications with hemodialysis. In some embodiments, at least two phenotypes comprises at least two of the following phenotypes: sexual attraction; pair bonding; personality traits; degree of relationship commitment or divorce potential; or pheromone perception.

In other embodiments of the gender specific health aspect, said reflex phenotype is reported when said individual has an increased predisposition or carrier status for said initial phenotype. In further embodiments, said reflex phenotype is reported when said individual has a decreased predisposition or carrier status for said initial phenotype. In another embodiment, said reflex phenotype is not reported if the individual has neither a decreased or increased predisposition or carrier status for said initial phenotype. In yet another embodiment, said reflex phenotype is reported concurrently with said initial phenotype. In an embodiment, said reflex phenotype is reported subsequently to said initial phenotype. In some embodiments, the determination of the predisposition or carrier status of the individual for said reflex phenotype is determined subsequently to the determination of the predisposition or carrier status of the individual for said initial phenotype. In other embodiments, said reflex phenotype is a disease that is positively correlated with said initial phenotype. In further embodiments, said initial phenotype is a disease and said reflex phenotype is a symptom of said disease. In another embodiment, said initial phenotype is a disease or disorder and reflex phenotype is a side effect of, or response to, a treatment for said initial phenotype.

In yet another embodiment of the gender specific health aspect, said initial phenotype is osteoporosis or osteoporotic fracture, and said reflex phenotype is one or more selected from the group consisting of: effects of specific diets on bone mineral density or osteoporosis; and effect of caffeine consumption on bone mineral density or osteoporosis. In an embodiment, said initial phenotype is obesity or leanness, and said reflex phenotype is one or more selected from the group consisting of: diabetes mellitus type II; amount of effort needed to lose weight; dyslipidemia or lipid levels with increased BMI or obesity; change in body fat or lipid levels with specific diets or with exercise; exercise tolerance, optimal exercise regimen, or athletic training regiment for weight management; and amount of weight retention post-pregnancy or degree of difficulty to lose weight post-pregnancy.

In some embodiments of the gender specific health aspect, said initial phenotype is heart disease, and said reflex phenotype is one or more selected from the group consisting of: dose required of statin to reduce risk of death or major cardiovascular events; level of severity of coronary atherosclerosis with CAD; degree of cognitive decline after coronary artery bypass graft surgery; restenosis following coronary angioplasty; statin-induced rhabdomyolysis or myopathy; acute coronary syndrome with preexisting coronary artery disease; suitability of anti-hyperlipidemic, anti-atherosclerotic or anti-restenosis medications or NSAIDs; effects of specific food or beverage consumption on risk of atherosclerosis or myocardial infarction; myocardial infarction with caffeine consumption; myocardial infarction with alcohol consumption; homocysteine level; coronary heart disease risk with the use of diuretics versus calcium channel blockers versus ACE inhibitors; C-reactive protein (CRP) level; stressful life events causing depressive symptoms, diagnosable depression, suicidality, or anxiety; and depression or seasonal affective disorder.

In other embodiments of the gender specific health aspect, said initial phenotype is thrombophilia or a thromboembolic disease, and said reflex phenotype is one or more selected from the group consisting of: warfarin suitability; and suitability of anti-thrombotic medications or NSAIDs. In further embodiments, said initial phenotype is cancer of female reproductive organs, and said reflex phenotype is one or more selected from the group consisting of: age of onset of breast cancer; suitability of medications used to treat breast or ovarian cancer; speed of tumor formation with breast or ovarian cancer; prognosis, mortality, receptor type, or stage with breast cancer; risk of breast or ovarian cancer with consumption of certain foods or vitamins; chemotherapy-induced leukemia; radiosusceptibility or residual DNA damage level to radiation; and response to chemotherapy to treat cervical cancer.

In another embodiment of the gender specific health aspect, said initial phenotype is skin cancer, and said reflex phenotype is one or more selected from the group consisting of: severity or prognosis of skin cancer; and suitability of medications used to treat skin cancer. In yet another embodiment, said initial phenotype is lung cancer, and said reflex phenotype is one or more selected from the group consisting of: association of lung cancer with the consumption of certain foods and vitamins; speed of tumor formation with lung cancer; suitability of medication used to treat lung cancer; lung cancer subtype, prognosis, or mortality; and radiosusceptibility or residual DNA damage level to radiation.

In an embodiment, said initial phenotype is Alzheimer's disease, and said reflex phenotype is one or more selected from the group consisting of: suitability of medications used to treat or delay the onset of Alzheimer's disease; aggressiveness or behavioral issues with Alzheimer's disease; age of onset of Alzheimer's disease; and symptomatology, prognosis, or rate of cognitive decline with Alzheimer's disease.

In some embodiments of the gender specific health aspect, said initial phenotype is colorectal cancer, and said reflex phenotype is one or more selected from the group consisting of: chemotherapy-induced leukemia; suitability of chemotherapeutic medications to treat colorectal cancer; speed of colorectal tumor formation, metastatic potential, prognosis, or mortality with colorectal cancer; colorectal cancer with consumption of specific food; colorectal cancer with exposure to tobacco smoke; and prognosis with colorectal cancer. In other embodiments, said initial phenotype is hypertension or blood pressure level, and said reflex phenotype is one or more selected from the group consisting of: effect of specific diets or consumption of specific foods or beverages on blood pressure; suitability of medications used to treat hypertension; carotid atherosclerosis due to hypertension; and kidney disease due to hypertension.

In further embodiments of the gender specific health aspect, said initial phenotype is polycystic ovary syndrome, and said reflex phenotype is one or more selected from the group consisting of: ovulatory response to Metformin treatment of polycystic ovary syndrome; hirsutism with polycystic ovary syndrome; and metabolic syndrome or impaired fasting glucose with polycystic ovary syndrome. In another embodiment, said initial phenotype is stroke, and said reflex phenotype is warfarin suitability. In yet another embodiment, said initial phenotype is myocardial infarction, and said reflex phenotype is one or more selected from the group consisting of: C-reactive protein levels (CRP); myocardial infarction with caffeine consumption; myocardial infarction with alcohol consumption; restenosis following coronary angioplasty; effects of consumption of specific foods or beverages on risk of myocardial infarction; degree of cognitive decline after coronary artery bypass graft surgery; suitability of anti-hyperlipidemic, anti-atherosclerotic, anti-restenosis medications, or NSAIDs; stressful life events causing depressive symptoms, diagnosable depression, suicidality, or anxiety; depression or seasonal affective disorder; and sudden cardiac death including cardiac arrhythmia or conduction abnormalities.

In an embodiment of the gender specific health aspect, said initial phenotype is breast cancer, and said reflex phenotype is one or more selected from the group consisting of: age of onset of breast cancer; suitability of medications used to treat breast cancer; speed of tumor formation with breast cancer; prognosis, mortality, receptor type, or stage with breast cancer; risk of breast or ovarian cancer with consumption of certain foods or vitamins; chemotherapy-induced leukemia; and radiosusceptibility or residual DNA damage level to radiation. In some embodiments, said initial phenotype is arrhythmmogenic right ventricular cardiomyopathy, and said reflex phenotype is one or more selected from the group consisting of: suitability of antiarrhythmogenic medication; and digoxin suitability. In other embodiments, said initial phenotype is hypertrophic cardiomyopathy, and said reflex phenotype is heart wall thickness with cardiomyopathy. In further embodiments, said initial phenotype is human immunodeficiency virus (HIV) susceptibility, and said reflex phenotype is one or more selected from the group consisting of: antiviral and HIV medication treatment suitability of drug; rate of progression, prognosis, CD4 count, or viral load with HIV infection; and HIV dementia.

In another embodiment of the gender specific health aspect, said initial phenotype is ovarian cancer, and said reflex phenotype is one or more selected from the group consisting of: risk of ovarian cancer with multivitamin supplements; suitability of medications used to treat ovarian cancer; chemotherapy-induced leukemia; and radiosusceptibility or residual DNA damage level to radiation. In yet another embodiment, said initial phenotype is male fertility or infertility, and said reflex phenotype is erectile dysfunction medication treatment effectiveness or sensitivity.

In an embodiment, said initial phenotype is cardiac arrhythmia or cardiac conduction abnormality, and said reflex phenotype is one or more selected from the group consisting of: cardiac arrhythmia or cardiac conduction abnormality and said reflex phenotype is one or more selected from the group consisting of: drug induced Torsade de Pointes; drug induced long QT syndrome; suitability of antiarrhythmogenic medication; digoxin suitability; age of onset of atrial fibrillation; and QTc length, severity of symptoms, and prognosis with long QT syndrome.

In some embodiments of the gender specific health aspect, said initial phenotype is cancer of male reproductive organs, and said reflex phenotype is one or more selected from the group consisting of: age of onset, stage, prognosis, survival, or aggressiveness of prostate cancer; suitability of medications used to treat prostate cancer; radiosusceptibility or residual DNA damage level to radiation; complications or adverse effects of radiotherapy for prostate cancer; suitability of medications to treat testicular cancer; relapse or prognosis with germ cell tumors; and prostate cancer associated with specific food consumption, vitamin intake or tobacco smoking. In other embodiments, said initial phenotype is melanoma, and said reflex phenotype is one or more selected from the group consisting of: severity or prognosis of melanoma; and toxicity, suitability of medications used to treat melanoma. In further embodiments, said initial phenotype is prostate cancer, and said reflex phenotype is one or more selected from the group consisting of: age of onset, stage, prognosis, survival, or aggressiveness of prostate cancer; effectiveness suitability of medications used to treat prostate cancer; radiosusceptibility or residual DNA damage level to radiation; complications or adverse effects of radiotherapy for prostate cancer; and prostate cancer associated with specific food consumption, vitamin intake or tobacco smoking.

In another embodiment of the gender specific health aspect, said initial phenotype is lumbar disc disease, and said reflex phenotype is metabolism, response to, suitability of opiates required for analgesic effect. In yet another embodiment, said initial phenotype is bladder cancer, kidney cancer or adrenal cancer, and said reflex phenotype is one or more selected from the group consisting of: metastasis, prognosis, or mortality from bladder cancer; and suitability of medications used to treat renal cell carcinoma. In an embodiment, said initial phenotype is IgA nephropathy, and said reflex phenotype is one or more selected from the group consisting of: effectiveness of ACE inhibitors in IgA nephropathy; and prognosis or progression of IgA nephropathy. In some embodiments, said initial phenotype is diabetic nephropathy, and said reflex phenotype is one or more selected from the group consisting of: severity of diabetic nephropathy; and risk of complications with hemodialysis.

In other embodiments of the gender specific health aspect, said predisposition or carrier status is determined from at least two genetic variants. In further embodiments, said at least two genetic variants are correlated with the same phenotype. In another embodiment, said predisposition or carrier status is determined for ovarian cancer and at least one of said genetic variants is selected from the group consisting of, or in linkage disequilibrium with at least one genetic variant selected from the group consisting of: rs6165, rs1466445, rs1042838, BRCA1 Chr. 17: 38529571-38529572 delAG, TP53 Chr. 17: 7520409-7520410 16 bp duplication, BRCA1 Chr. 17: 38462605-38462606 insC, BRCA1 Chr. 17: 38498069 delA, BRCA1 Chr. 17: 38497040 delA, BRCA1 Chr. 17: 38497006-38497009 delTCAA, BRCA1 Chr. 17: 38499861-38499900 40 bp deletion, BRCA1 Chr. 17: 38497973-38497974 insTGAGA, BRCA1 Chr. 17: 38487977 Y, rs1800709, BRCA1 Chr. 17: 38521288 K, rs28897749, rs2854344, rs2273535, and rs6166. In yet another embodiment, said predisposition or carrier status is determined for prostate cancer and at least one of said genetic variants is selected from the group consisting of, or in linkage disequilibrium with at least one genetic variant selected from the group consisting of: rs4430796, rs11649743, rs6983267, rs16901979, rs6465657, rs1447295, rs5945572, rs721048, rs4242384, rs5945619, rs1799950, rs3842752, AR Chr. X: 66681885-66681950 CAG trinucleotide repeat, AR Chr. X: 66854051 K, rs10486567, rs1859962, rs16260, rs10086908, rs6983561, and rs9364554.

In an embodiment of the gender specific health aspect, said individual selects said two or more phenotypes. In some embodiments, said set of genetic variants was identified using a high density DNA microarray. In other embodiments, said set of genetic variants was identified by sequencing genomic DNA from said individual. In further embodiments, said individual is of the female gender. In another embodiment, said individual is of the male gender.

Another second aspect of gender specific health provided herein is a gender specific health set of probes, wherein said set comprises probes, wherein each of said probes is specifically selected to detect a genetic variant correlated with a gender-specific health phenotype. In some embodiments of the gender-specific health set of probes, said set detects at least two phenotypes listed in the following figures: Women\'s Health Panel Alpha (FIG. 19), Women\'s Health Panel Beta (FIG. 20), Female Fertility Panel (FIG. 30) Gynecology Panel (FIG. 56), Polycystic Ovary Syndrome Panel (FIG. 128), Men\'s Health Panel Alpha (FIG. 21), Men\'s Health Panel Beta (FIG. 22), Male Fertility & Erectile Function Panel (FIG. 31), Urology & Nephrology Panel (FIG. 61), Sexuality, Mate Selection, Relationships and Marriage/Divorce Panel (FIG. 36). In other embodiments, the gender-specific health set of probes, said set comprises at least two probes, and each of said at least two probes detects a different genetic variant, and wherein each of said different genetic variants is correlated to the same phenotype.

Another aspect provided herein is related to Medical Care phenotypes and is a method of determining the predisposition or carrier status of an individual for two or more Medical Care phenotypes comprising: identifying by nucleic acid array, sequencing apparatus, or nanopore sequencer a set of genetic variants in an individual, wherein each of said genetic variants is correlated with a medical care phenotype; using a computer to determine the predisposition or carrier status of said individual for at least two phenotypes, wherein said predisposition or carrier status is based on said set of genetic variants; providing a report of said predisposition or carrier status to said individual, to a health care provider of said individual, or to a third party; and, optionally, (d) combining the predisposition or carrier status of said individual for said at least two phenotypes into a Medical Care score, wherein said score is reported to said individual, to a health care provider of said individual, or to a third party.

In an embodiment of the medical care aspect, at least two phenotypes comprise an initial phenotype and a reflex phenotype, wherein said reflex phenotype is a phenotype that is not the initial phenotype, and wherein the reporting of the predisposition or carrier status of said individual for the reflex phenotype depends on the outcome of said determination of predisposition or carrier status of said individual for the first phenotype. In some embodiment, at least two phenotypes are at least two phenotypes listed in one or more of the following figures: Emergency Panel (FIG. 46), Surgery & Anesthesiology Panel (FIG. 54), Transplant Panel (FIG. 55), Kidney Transplant Panel (FIG. 132), Liver Transplant Panel (FIG. 133), Lung Transplant Panel (FIG. 134), Stem Cell Transplant Panel (FIG. 135), Interventional Radiology Panel (FIG. 144); Pathology & Tissue Repository Panel (FIG. 139), Research & Clinical Trial Panel (FIG. 141), Pharmacology & Alternative Medication Panel (FIG. 90), Pain Panel (FIG. 92), and Death/Autopsy Panel (FIG. 149). In other embodiments, at least two phenotypes comprises at least five phenotypes. In another embodiment, at least two phenotypes comprise: at least one phenotype that follows monogenic inheritance; and at least one phenotype that follows multifactorial or polygenic inheritance.

In other embodiments of the medical care aspect, at least two phenotypes comprises at least two of the following phenotypes: prognosis or survival following kidney transplant; human leukocyte antigen typing; blood group; malignant hyperthermia; postanesthetic apnea; thrombophilia or thromboembolic disease; bleeding diathesis, coagulation disorders, or hemophilia; and wound dehiscence. In further embodiments, at least two phenotypes comprises at least two of the following phenotypes: prognosis or survival following liver transplant; human leukocyte antigen typing; blood group; malignant hyperthermia; postanesthetic apnea; thrombophilia or thromboembolic disease; bleeding diathesis, coagulation disorders, or hemophilia; and wound dehiscence. In another embodiment, at least two phenotypes comprises at least two of the following phenotypes: prognosis or survival following lung transplant; human leukocyte antigen typing; blood group; malignant hyperthermia; postanesthetic apnea; thrombophilia or thromboembolic disease; bleeding diathesis, coagulation disorders, or hemophilia; and wound dehiscence.

In yet another embodiment of the medical care aspect, at least two phenotypes comprises at least two of the following phenotypes: prognosis or survival following stem cell transplant; graft versus host disease; human leukocyte antigen typing; blood group; and susceptibility to bacteremia, sepsis, septic shock, severe sepsis, or systemic inflammatory response syndrome. In an embodiment, at least two phenotypes comprises at least two of the following phenotypes: thrombophilia or thromboembolic disease; bleeding diathesis, coagulation disorders, or hemophilia; allergic reactions; seizures or epilepsy; latex allergy; or medication metabolism. In some embodiments, at least two phenotypes comprises at least two of the following phenotypes: universal identifier; lineage or ancestry information; medication suitability; cancer; or heart disease. In other embodiments, at least two phenotypes comprises at least two of the following phenotypes: medication suitability; cardiac arrhythmia or cardiac conduction abnormality; universal identifier or identity testing; ethnicity, lineage, or ancestry information; blood group; or vitamin, mineral, element, herbal or nutritional supplement suitability; cancer; heart disease; bleeding diathesis; coagulation disorders; thrombophilia; neurodegenerative disease; or medication metabolism or suitability.

In further embodiments of the medical care aspect, at least two phenotypes comprises at least two of the following phenotypes: drug suitability; taste perception; or vitamin, mineral, element, herbal or nutritional supplement suitability. In another embodiment, at least two phenotypes comprises at least two of the following phenotypes: pain tolerance; analgesic or pain medicine suitability; depression or seasonal affective disorder; fibromyalgia; stressful life events causing depressive symptoms, diagnosable depression, suicidality, or anxiety; or suicidality. In yet another embodiment, at least two phenotypes comprises at least two of the following phenotypes: Wolff-Parkinson-White syndrome; long QT syndrome; arrhythmogenic right vectricular cardiomyopathy; brugada syndrome; ventricular fibrillation; ventricular tachycardia; sudden infant death syndrome; heart block; atrial fibrillation; drug-induced long QT syndrome; drug-induced torsade de pointes; or thrombophilia or thromboembolic disease.

In an embodiment of the medical care aspect, wherein said at least two phenotypes comprise an initial phenotype and a reflex phenotype, said reflex phenotype is reported when said individual has an increased predisposition or carrier status for said initial phenotype. In some embodiments, said reflex phenotype is reported when said individual has a decreased predisposition or carrier status for said initial phenotype. In other embodiments, said reflex phenotype is not reported if the individual has neither a decreased or increased predisposition or carrier status for said initial phenotype. In further embodiments, said reflex phenotype is reported concurrently with said initial phenotype. In another embodiment, said reflex phenotype is reported subsequently to said initial phenotype.

In an embodiment, wherein at least two phenotypes comprise an initial phenotype and a reflex phenotype, wherein said reflex phenotype is a phenotype that is not the initial phenotype, and wherein the reporting of the predisposition or carrier status of said individual for the reflex phenotype depends on the outcome of said determination of predisposition or carrier status of said individual for the first phenotype, wherein the determination of the predisposition or carrier status of the individual for said reflex phenotype is determined subsequently to the determination of the predisposition or carrier status of the individual for said initial phenotype.

In some embodiments of the medical care aspect, said reflex phenotype is a disease that is positively correlated with said initial phenotype. In other embodiments, said initial phenotype is a disease and said reflex phenotype is a symptom of said disease. In further embodiments, said initial phenotype is a disease or disorder and reflex phenotype is a side effect of, or response to, a treatment for said initial phenotype. In another embodiment, said initial phenotype is cardiac arrhythmia or cardiac conduction abnormality, and said reflex phenotype is one or more selected from the group consisting of: drug-induced torsade de pointes; drug-induced long QT syndrome; suitability of antiarrhythmogenic medication; digoxin suitability; age of onset of atrial fibrillation; QTc length, severity, symptoms, and prognosis with long QT syndrome. In yet another embodiment, said initial phenotype is hypertrophic cardiomyopathy, and said reflex phenotype is heart wall thickness with cardiomyopathy. In an embodiment, said initial phenotype is thrombophilia or a thromboembolic disorder, and said reflex phenotype is one or more selected from the group consisting of: warfarin suitability; and suitability of anti-thrombotic medications or NSAIDs.

In some embodiments of the medical care aspect, said initial phenotype is susceptibility to bacteremia, sepsis, severe sepsis, septic shock, or systemic inflammatory response syndrome, and said reflex phenotype is one or more selected from the group consisting of: severity of sepsis, septic shock, severe sepsis or systemic inflammatory response syndrome; and source of infection, type of bacteria with bacteremia, sepsis, severe sepsis, septic shock or systemic inflammatory response syndrome. In other embodiments, said initial phenotype is arrhythmogenic right ventricular cardiomyopathy, and said reflex phenotype is one or more selected from the group consisting of: suitability of antiarrhythmogenic medication; and digoxin suitability. In further embodiments, said initial phenotype is allergic reactions, and said reflex phenotype is anti-allergy medication suitability. In another embodiment, said initial phenotype is seizures or epilepsy, and said reflex phenotype is suitability of antiepileptic medication.

In yet another embodiment of the medical care aspect, said initial phenotype is cancer and said reflex phenotype is one or more selected from the group consisting of: age of onset of breast cancer; speed of tumor formation with breast cancer; prognosis, mortality, receptor type, or stage with breast cancer; risk of breast or ovarian cancer with consumption of certain foods or vitamins; chemotherapy-induced leukemia; radiosusceptibility or residual DNA damage level to radiation; age of onset, stage, prognosis, survival or aggressiveness of prostate cancer; prognosis with colorectal cancer; colorectal cancer with consumption of specific food; colorectal cancer with exposure to tobacco smoke; subtype, prognosis, or mortality of lung cancer; severity or prognosis of melanoma; lymph node metastasis, prognosis, or survival with gastric cancer; prognosis or survival with gastroenteropancreatic neuroendocrine tumors; disease outcome or survival with leukemia; prognosis with tongue cancer; prognosis with head or neck cancer; metastasis, prognosis or mortality from bladder cancer; cancer with alcohol consumption; survival or prognosis with brain cancer; prostate cancer associated with specific food consumption, vitamin intake or tobacco smoking; and venous thromboembolism associated with thalidomide treatment.

In an embodiment of the medical care aspect, said initial phenotype is heart disease, and said reflex phenotype is one or more selected from the group consisting of: dose required of statin to reduce risk of death or major cardiovascular events; level of severity of coronary atherosclerosis with CAD; degree of cognitive decline after coronary artery bypass graft surgery; restenosis following coronary angioplasty; statin-induced rhabdomyolysis or myopathy; acute coronary syndrome with preexisting coronary artery disease; suitability of anti-hyperlipidemic, anti-atherosclerotic or anti-restenosis medications or NSAIDs; effects of specific food or beverage consumption on risk of atherosclerosis or myocardial infarction; myocardial infarction with caffeine consumption; myocardial infarction with alcohol consumption; homocysteine level; coronary heart disease risk with the use of diuretics versus calcium channel blockers versus ACE inhibitors; C-reactive protein (CRP) level; stressful life events causing depressive symptoms, diagnosable depression, suicidality, or anxiety; and depression or seasonal affective disorder.

In some embodiments of the medical care aspect, said initial phenotype is depression or seasonal affective disorder and said reflex phenotype is one or more selected from the group consisting of: suitability of medications used to treat depression; treatment-emergent suicidality during treatment with antidepressants; response to treatment for depression; and suitability of medication for treatment of anxiety. In other embodiments said initial phenotype is stressful life events causing depressive symptoms diagnosable depression or anxiety, and said reflex phenotype is one or more selected from the group consisting of: suitability of medications used to treat depression; treatment-emergent suicidality during treatment with antidepressants; and effectiveness and choice of medication for treatment for anxiety. In further embodiments, said initial phenotype is atrial fibrillation, and said reflex phenotype is age of onset of atrial fibrillation.

In an embodiment of a method of determining the predisposition or carrier status of an individual for two or more phenotypes related to Medical Care, said predisposition or carrier status is determined from at least two genetic variants. In some embodiments, at least two genetic variants are correlated with the same phenotype. In other embodiments, said predisposition or carrier status is determined for colorectal cancer and at least one of said genetic variants is selected from the group consisting of, or in linkage disequilibrium with, at least one genetic variant selected from the group consisting of: rs3802842, rs4939827, rs10795668, rs2032582, rs1801166, rs4779584, MLH1 Chr3: 37061073-37064610 3.5 kb deletion, rs6983267, rs7014346, rs4430796, rs11649743, rs266729, rs2066844, rs1801155, rs1042522, TP53 Chr. 17: 7520409-7520410 16 bp duplication, rs10505477, rs1801133, rs266729, rs719725, rs16892766, rs11466445, and rs7903146. In further embodiments, said predisposition or carrier status is determined for sensitivity to opiates and at least one of said genetic variants is selected from the group consisting of, or in linkage disequilibrium with, at least one genetic variant selected from the group consisting of: rs1805007, rs1805008, rs1799971, rs1135840, and rs3892097.

In an embodiment, a method of determining the predisposition or carrier status of an individual for two or more phenotypes related to Medical Care is provided, wherein said individual selects said two or more phenotypes. In some embodiments, said set of genetic variants was identified using a high density DNA microarray. In other embodiments, said set of genetic variants was identified by sequencing genomic DNA from said individual. In further embodiments, said individual is a patient. In another embodiment, said individual is a suffering from an unknown disease or condition. In yet another embodiment, said individual is an organ, cell, or tissue transplant candidate. In another embodiment, said individual has died of unknown causes.

In another medical care aspect, a medical care set of probes is provided, wherein said set comprises probes, wherein each of said probes is specifically selected to detect a genetic variant correlated with a medical care phenotype. In an embodiment of the medical care set of probes, said set detects at least two phenotypes listed in the following figures: Emergency Panel (FIG. 46), Surgery & Anesthesiology Panel (FIG. 54), Transplant Panel (FIG. 55), Kidney Transplant Panel (FIG. 132), Liver Transplant Panel (FIG. 133), Lung Transplant Panel (FIG. 134), Stem Cell Transplant Panel (FIG. 135), Interventional Radiology Panel (FIG. 144); Pathology & Tissue Repository Panel (FIG. 139), Research & Clinical Trial Panel (FIG. 141), Pharmacology & Alternative Medication Panel (FIG. 90), Pain Panel (FIG. 92), and Death/Autopsy Panel (FIG. 149). In some embodiments of the medical care set of probes, said set comprises at least two probes, and each of said at least two probes detects a different genetic variant, and wherein each of said different genetic variants is correlated to the same phenotype.

In third medical care aspect, a method is provided comprising: obtaining by nucleic acid array, sequencing apparatus, or nanopore sequencer a set of genetic variants for one or more subjects, wherein said one or more subjects have been or are contemplated to be in a clinical drug efficacy or safety trial, and wherein each member of said set of genetic variants is identified with each of said one or more subjects and wherein each member of said set of genetic variants is also correlated with a phenotype; obtaining clinical trial results data for said one or more subjects, or providing clinical trial results data previously obtained for said one or more subjects, wherein each of said clinical trial results are identified with each of said one or more subjects; and using a computer to correlate the clinical trial results identified with each subject with the set of genetic variants identified with each subject; wherein the step of correlating identifies one or more of said genetic variants that are predictive for one or more of said clinical trial results. In an embodiment of the method, the method further comprises identifying one or more subsets of subjects that have a set of genetic variants that provide an increased chance of a positive or negative clinical trial result. In some embodiments, said clinical trial results indicate the level of safety of said clinical drug. In other embodiments, said clinical trial results indicate the level of effectiveness of said clinical drug. In further embodiments, said clinical trial results indicate the degree of adverse effects of said clinical drug.

In another embodiment of the third medical care aspect, said set of genetic variants comprises one or more genetic variants correlated with a phenotype listed in the Research & Clinical Trial Panel (FIG. 141). In yet another embodiment, said set of genetic variants comprises one or more genetic variants correlated with one or more of the following phenotypes: medication suitability; cardiac arrhythmia or cardiac conduction abnormality; universal identifier or identity testing; ethnicity, lineage, or ancestry information; blood group; or vitamin, mineral, element, herbal or nutritional supplement suitability; cancer; heart disease; bleeding diathesis; coagulation disorders; thrombophilia; or neurodegenerative disease. In an embodiment, said set of genetic variants comprises one or more genetic variants correlated with: medication suitability; and one or more of the following phenotypes: cardiac arrhythmia or cardiac conduction abnormality; universal identifier or identity testing; ethnicity, lineage, or ancestry information; blood group; or vitamin, mineral, element, herbal or nutritional supplement suitability; cancer; heart disease; bleeding diathesis; coagulation disorders; thrombophilia; or neurodegenerative disease. In some embodiments, said set of genetic variants comprises one or more genetic variants correlated with: a universal identifier; and one or more of the following phenotypes: cardiac arrhythmia or cardiac conduction abnormality; ethnicity, lineage, or ancestry information; blood group; or vitamin, mineral, element, herbal or nutritional supplement suitability; cancer; heart disease; bleeding diathesis; coagulation disorders; thrombophilia; neurodegenerative disease; or medication suitability.

Another aspect provided herein is related to longevity phenotypes and is a method of determining the predisposition or carrier status of an individual for two or more longevity phenotypes comprising: identifying by nucleic acid array, sequencing apparatus, or nanopore sequencer a set of genetic variants in an individual, wherein each of said genetic variants is correlated with a longevity phenotype; using a computer to determine the predisposition or carrier status of said individual for at least two phenotypes, wherein said predisposition or carrier status is based on said set of genetic variants; providing a report of said predisposition or carrier status to said individual, to a health care provider of said individual, or to a third party; and optionally combining the predisposition or carrier status of said individual for said at least two phenotypes into a longevity score, wherein said score is reported to said individual, to a health care provider, or to a third party.

In other embodiments of the longevity phenotype aspect, at least two phenotypes comprise at least five phenotypes. In further embodiments, at least two phenotypes comprise: at least one phenotype that follows monogenic inheritance; and at least one phenotype that follows multifactorial or polygenic inheritance. In another embodiment, at least two phenotypes comprises at least two of the following phenotypes: heart disease; hypertension or blood pressure level; cardiac arrhythmia or cardiac conduction abnormality; thrombophilia or thromboembolic disease; cardiomyopathy; heart failure; peripheral arterial disease; or structural heart defect.

In yet another embodiment of the longevity phenotype aspect, at least two phenotypes comprises at least two of the following phenotypes: coronary artery disease (CAD); myocardial infarction; thrombophilia and thromboembolic disease; Wolff-Parkinson-White syndrome; atrial fibrillation; hypertrophic cardiomyopathy; arrhythmogenic right ventricular cardiomyopathy; dyslipidemia; hypertension or blood pressure level; heart failure; dilated cardiomyopathy; coronary artery spasm; aortic or arterial aneurysm or dissection; effects of specific foods or beverages consumption on heart health, risk of atherosclerosis, or risk of myocardial infarction; long QT syndrome; or brugada syndrome. In an embodiment, at least two phenotypes comprises at least two of the following phenotypes: heart failure; survival or prognosis with congestive heart failure; thrombophilia or thromboembolic disease; or heart disease. In some embodiments, at least two phenotypes comprises at least two of the following phenotypes: coronary artery disease (CAD); suitability of anti-hyperlipidemic, anti-atherosclerotic, antiplatelet or anti-restenosis medications or NSAIDs; risk of acute coronary syndrome with preexisting coronary artery disease; degree of cognitive decline after coronary artery bypass graft surgery; restenosis following coronary angioplasty; statin-induced rhabdomyolysis or myopathy; level of severity of coronary atherosclerosis with CAD; association of specific food or beverage consumption on risk of atherosclerosis or myocardial infarction; or homocysteine level.

In other embodiments of the longevity phenotype aspect, at least two phenotypes comprises at least two of the following phenotypes: myocardial infarction; suitability of anti-hyperlipidemic, anti-atherosclerotic, antiplatelet or anti-restenosis medications or NSAIDs; restenosis following coronary angioplasty; degree of cognitive decline after coronary artery bypass graft surgery; sudden cardiac death; stressful life events causing depressive symptoms, diagnosable depression, suicidality, or anxiety; and association of specific food or beverage consumption on risk of atherosclerosis or myocardial infarction. In further embodiments, at least two phenotypes comprises at least two of the following phenotypes: atrial fibrillation; long QT syndrome; drug-induced long QT syndrome; drug-induced torsade de pointes; ventricular fibrillation; ventricular tachycardia; arrhythmogenic right ventricular cardiomyopathy; Wolff-Parkinson-White syndrome; brugada syndrome; heart block; suitability of antiarrhythmogenic medication; digoxin suitability; or thrombophilia or thromboembolic disease. In another embodiment, at least two phenotypes comprises at least two of the following phenotypes: blood group and hemoglobin variants; anemia or abnormalities of the blood; thrombophilia or thromboembolic disease; bleeding diathesis, coagulation disorder, or hemophilia; thalassemia; sickle cell anemia or sickle cell trait; malaria susceptibility; or universal identifier or identity testing.

In yet another embodiment of the longevity phenotype aspect, at least two phenotypes comprises at least two of the following phenotypes: dyslipidemia; dosage required of statin to reduce death or major cardiovascular events; statin-induced rhabdomyolysis or myopathy; change in body fat, lipid levels with specific diets or exercise; risk of acute coronary syndrome with preexisting coronary artery disease; suitability of anti-hyperlipidemic, anti-atherosclerotic, or anti-restenosis medication; severity of coronary atherosclerosis with coronary artery disease; degree of cognitive decline after coronary artery bypass graft surgery; or restenosis following coronary angioplasty. In an embodiment, at least two phenotypes comprises at least two of the following phenotypes: lipid levels or dyslipidemia; anti-hyperlipidemic, anti-atherosclerotic, or anti-restenosis medication suitability; change in body fat or lipid levels on specific diets or with exercise; level of severity of coronary atherosclerosis; coronary artery disease (CAD); or myocardial infarction. In some embodiments, at least two phenotypes comprises at least two of the following phenotypes: hypertension or blood pressure level; suitability of medications used to treat hypertension; association of specific diets or consumption of specific foods or beverages on blood pressure; carotid atherosclerosis to due hypertension; or kidney disease due to hypertension.

In other embodiments of the longevity phenotype aspect, at least two phenotypes comprises at least two of the following phenotypes: stroke; intracranial aneurysm; warfarin suitability; antithrombotic effectiveness of acetylsalicylic acid; thrombophilia or thromboembolic disease; or atrial fibrillation. In further embodiments, at least two phenotypes comprises at least two of the following phenotypes: thrombophilia or thromboembolic disease; warfarin suitability; suitability of anti-hyperlipidemic, anti-atherosclerotic, antiplatelet medication, anti-restenosis medication, or NSAIDs; stroke; myocardial infarction; or coronary artery disease (CAD). In another embodiment, at least two phenotypes comprises at least two of the following phenotypes: longevity or lifespan; heart disease; cardiac arrhythmia or cardiac conduction abnormality; arrhythmias; cancer; thrombophilia or thromboembolic disease; or infectious disease susceptibility. In yet another embodiment, at least two phenotypes comprises at least two of the following phenotypes: longevity or lifespan; myocardial infarction; stroke; arrhythmogenic right ventricular cardiomyopathy; Wolff-Parkinson-White syndrome; malignant hyperthermia; lung cancer; breast cancer; colorectal cancer; human immunodeficiency virus (HIV) susceptibility; or long QT syndrome.

In an embodiment of the longevity phenotype aspect, at least two phenotypes comprises at least two of the following phenotypes: longevity or lifespan; heart disease; cancer; chronic, degenerative, or fatal neurologic disease; cardiac arrhythmia or cardiac conduction abnormality; stroke; suitability of medications; rare disease, orphan diseases, metabolic disorders or syndromes; or psychiatric illness. In some embodiments, at least two phenotypes comprises at least two of the following phenotypes: longevity or lifespan; myocardial infarction; lung cancer; diabetes mellitus type II or insulin resistance; multiple sclerosis; Crohn\'s disease; fibromyalgia; stroke; or Alzheimer\'s disease. In other embodiments, at least two phenotypes comprises at least two of the following phenotypes: specific physical exercise regimen for most efficient physical exercise; obesity or leanness; genetic age and effectiveness of current or past exercise regimens; effects of specific diets or exercise on obesity, BMI, adiposity, bone mineral density, lipid levels, or insulin resistance; reduced sleep quality and insomnia due to caffeine consumption; whether or not testosterone doping may be detected on a drug screen; muscle strength in arms and legs; physical function in older age; or longevity or lifespan.

In further embodiments of the longevity phenotype aspect, at least two phenotypes comprises at least two of the following phenotypes: prognosis following head injury or brain injury; athletic ability or predisposition to specific sports; hypertrophic cardiomyopathy; arrhythmogenic right ventricular cardiomyopathy; whether or not testosterone doping may be detected on a drug screen; or athletic ability or predisposition to specific sports, athletic performance, or risk from physical activity. In another embodiment, at least two phenotypes comprises at least two of the following phenotypes: obesity or leanness; diabetes type II or insulin resistance; change in body fat of lipid levels with specific diets or with exercise; exercise tolerance, optimal exercise regimen, or athletic training regimen for weight management; amount of effort needed to lose weight; amount of food consumption; lipid levels associated with increased BMI or obesity; or depression or seasonal affective disorder.

In yet another embodiment of the longevity phenotype aspect, at least two phenotypes comprises at least two of the following phenotypes: obesity or leanness; effects of specific diets on weight, obesity, BMI, or adiposity; effects of physical exercise on weight, obesity, BMI, or adiposity; specific physical exercise regimens for most efficient physical exercise; effects of exercise on lipid levels; effects of specific diets on bone mineral density; effects of specific diets on lipid levels; effects of specific diets on blood pressure; cancer risk with consumption of specific foods, beverages, alcohol, or medications; effects of specific foods or beverage consumption on heart health, risk of atherosclerosis, or risk of myocardial infarction; vitamin, mineral, element, or herbal or nutritional supplement suitability or deficiency of; taste perception or specific food preference; or effectiveness of Sibutramine for weight reduction. In an embodiment, at least two phenotypes comprises at least two of the following phenotypes: obesity or leanness; effects of specific diets on weight, obesity, BMI, or adiposity; taste perception or specific food preference; effectiveness of Sibutramine for weight reduction; association of colorectal cancer with consumption of specific food; effects of specific diets on bone mineral density; effects of specific diets on lipid levels; effects of specific diets on blood pressure; effects of specific foods or beverage consumption on heart health, risk of atherosclerosis, or risk of myocardial infarction; or vitamin, mineral, element, or herbal or nutritional supplement suitability or deficiency of.

In further embodiments of the longevity phenotype aspect, said reflex phenotype is reported when said individual has an increased predisposition or carrier status for said initial phenotype. In another embodiment, said reflex phenotype is reported when said individual has a decreased predisposition or carrier status for said initial phenotype. In yet another embodiment, said reflex phenotype is not reported if the individual has neither a decreased or increased predisposition or carrier status for said initial phenotype. In some embodiments, said reflex phenotype is reported concurrently with said initial phenotype. In other embodiments, said reflex phenotype is reported subsequently to said initial phenotype. In further embodiments, the determination of the predisposition or carrier status of the individual for said reflex phenotype is determined subsequently to the determination of the predisposition or carrier status of the individual for said initial phenotype. In another embodiment, said reflex phenotype is a disease that is positively correlated with said initial phenotype.

In yet another embodiment of the longevity phenotype aspect, said initial phenotype is a disease and said reflex phenotype is a symptom of said disease. In an embodiment, said initial phenotype is a disease or disorder and reflex phenotype is a side effect of, or response to, a treatment for said initial phenotype. In some embodiments, said initial phenotype is heart disease, and said reflex phenotype is one or more selected from the group consisting of: dose required of statin to reduce risk of death or major cardiovascular events; level of severity of coronary atherosclerosis with coronary artery disease (CAD); degree of cognitive decline after coronary artery bypass graft surgery; restenosis following coronary angioplasty; statin-induced rhabdomyolysis or myopathy; acute coronary syndrome with preexisting coronary artery disease; suitability of anti-hyperlipidemic, anti-atherosclerotic antiplatelet or anti-restenosis medications or NSAIDs; effects of specific food or beverage consumption on risk of atherosclerosis or myocardial infarction; myocardial infarction with caffeine consumption; myocardial infarction with alcohol consumption; homocysteine level; coronary heart disease risk with the use of diuretics versus calcium channel blockers versus ACE inhibitors; C-reactive protein (CRP) level; stressful life events causing depressive symptoms, diagnosable depression, suicidality, or anxiety; and depression or seasonal affective disorder.

In other embodiments of the longevity phenotype aspect, said initial phenotype is heart disease, and said reflex phenotype is one or more selected from the group consisting of: effect of specific diets or consumption of specific foods or beverages on blood pressure; suitability of medications used to treat hypertension; carotid atherosclerosis due to hypertension; and kidney disease due to hypertension. In further embodiments, said initial phenotype is cardiac arrhythmia or cardiac conduction abnormality, and said reflex phenotype is one or more selected from the group consisting of: drug-induced torsade de pointes; drug-induced long QT syndrome; suitability of antiarrhythmogenic medication; digoxin suitability; age of onset of atrial fibrillation; QTc length, severity, symptoms, and prognosis with long QT syndrome. In another embodiment, said initial phenotype is thrombophilia or a thromboembolic disorder, and said reflex phenotype is one or more selected from the group consisting of: warfarin suitability; and suitability of anti-thrombotic medications or NSAIDs. In yet another embodiment, said initial phenotype is cardiomyopathy, and said reflex phenotype is heart wall thickness with cardiomyopathy.

In an embodiment of the longevity phenotype aspect, said initial phenotype is heart failure, and said reflex phenotype is one or more selected from the group consisting of: effectiveness or therapeutic response or choice of interventions with heart failure; survival or prognosis with congestive heart failure; and suitability of medications to treat heart failure. In some embodiments, said initial phenotype is coronary artery disease (CAD), and said reflex phenotype is one or more selected from the group consisting of: dose required of statin to reduce risk of death or major cardiovascular events; level of severity of coronary atherosclerosis with CAD; degree of cognitive decline after coronary artery bypass graft surgery; restenosis following coronary angioplasty; statin-induced rhabdomyolysis or myopathy; acute coronary syndrome with preexisting coronary artery disease; suitability of anti-hyperlipidemic, anti-atherosclerotic, antiplatelet or anti-restenosis medications, or NSAIDs; effects of specific food or beverage consumption on risk of myocardial infarction.

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